Epidemiology

Prevalence of hepatitis B virus as of 2005

In 2004, an estimated 350 million individuals were infected worldwide. National and regional
prevalences range from over 10% in Asia to under 0.5% in the United States and Northern
Europe.

Routes of infection include vertical transmission (such as through childbirth), early life
horizontal transmission (bites, lesions, and sanitary habits), and adult horizontal transmission
(sexual contact, intravenous drug use).[96]

The primary method of transmission reflects the prevalence of chronic HBV infection in a given
area. In low prevalence areas such as the continental United States and Western Europe, injection
drug abuse and unprotected sex are the primary methods, although other factors may also be
important.[97] In moderate prevalence areas, which include Eastern Europe, Russia, and Japan,
where 2–7% of the population is chronically infected, the disease is predominantly spread among
children. In high-prevalence areas such as China and South East Asia, transmission during
childbirth is most common, although in other areas of high endemicity such as Africa,
transmission during childhood is a significant factor.[98] The prevalence of chronic HBV
infection in areas of high endemicity is at least 8% with 10–15% prevalence in Africa/Far
East.[99] As of 2010, China has 120 million infected people, followed by India and Indonesia with
40 million and 12 million, respectively. According to World Health Organization (WHO), an
estimated 600,000 people die every year related to the infection.[100]

In the United States about 19,000 new cases occurred in 2011 down nearly 90% from 1990.[64]

History
The hepatitis B virus has infected humans since at least the Bronze Age.[101][102] The evidence
was obtained from 4,500-year-old human remains.[102] According to the 2018 study, the viral
genomes obtained by shotgun sequencing became the oldest ever recovered from vertebrate
samples.[102] It was also found that some ancient hepatitis viral strains still infect humans, while
other became extinct.[102] This disproved the belief that hepatitis B originated in the New World
and spread to Europe around 16th century.[102] Another 2018 study of the remains of a
mummified child found in the Basilica of San Domenico Maggiore in Naples concluded that the
child, who had lived in the 16th century, had a form of HBV, and that the virus was closely
related to modern variants.[103]
The earliest record of an epidemic caused by hepatitis B virus was made by Lurman in 1885.[104]
An outbreak of smallpox occurred in Bremen in 1883 and 1,289 shipyard employees were
vaccinated with lymph from other people. After several weeks, and up to eight months later, 191
of the vaccinated workers became ill with jaundice and were diagnosed as suffering from serum
hepatitis. Other employees who had been inoculated with different batches of lymph remained
healthy. Lurman's paper, now regarded as a classical example of an epidemiological study,
proved that contaminated lymph was the source of the outbreak. Later, numerous similar
outbreaks were reported following the introduction, in 1909, of hypodermic needles that were
used, and, more importantly, reused, for administering Salvarsan for the treatment of syphilis.
The virus was not discovered until 1966 when Baruch Blumberg, then working at the National
Institutes of Health (NIH), discovered the Australia antigen (later known to be hepatitis B
surface antigen, or HBsAg) in the blood of Aboriginal Australian people.[105] Although a virus
had been suspected since the research published by Frederick MacCallum in 1947,[106] David
Dane and others discovered the virus particle in 1970 by electron microscopy.[107] By the early
1980s the genome of the virus had been sequenced,[108] and the first vaccines were being
tested.[109]
Cause
Transmission

Transmission of hepatitis B virus results from exposure to infectious blood or body fluids
containing blood. It is 50 to 100 times more infectious than human immunodeficiency virus
(HIV).[28] Possible forms of transmission include sexual contact,[29] blood transfusions and
transfusion with other human blood products,[30] re-use of contaminated needles and syringes,[31]
and vertical transmission from mother to child (MTCT) during childbirth. Without intervention,
a mother who is positive for HBsAg has a 20% risk of passing the infection to her offspring at
the time of birth. This risk is as high as 90% if the mother is also positive for HBeAg. HBV can
be transmitted between family members within households, possibly by contact of nonintact skin
or mucous membrane with secretions or saliva containing HBV.[32] However, at least 30% of
reported hepatitis B among adults cannot be associated with an identifiable risk factor.[33]
Breastfeeding after proper immunoprophylaxis does not appear to contribute to mother-to-child-
transmission (MTCT) of HBV.[34] The virus may be detected within 30 to 60 days after infection
and can persist and develop into chronic hepatitis B. The incubation period of the hepatitis B
virus is 75 days on average but can vary from 30 to 180 days.[35]

Virology
Main article: Hepatitis B virus

Structure

The structure of hepatitis B virus

Hepatitis B virus (HBV) is a member of the hepadnavirus family.[36] The virus particle (virion)
consists of an outer lipid envelope and an icosahedral nucleocapsid core composed of protein.
These virions are 30–42 nm in diameter. The nucleocapsid encloses the viral DNA and a DNA
polymerase that has reverse transcriptase activity.[37] The outer envelope contains embedded
proteins that are involved in viral binding of, and entry into, susceptible cells. The virus is one of
the smallest enveloped animal viruses. The 42 nm virions, which are capable of infecting liver
cells known as hepatocytes, are referred to as "Dane particles".[38] In addition to the Dane
particles, filamentous and spherical bodies lacking a core can be found in the serum of infected
individuals. These particles are not infectious and are composed of the lipid and protein that
forms part of the surface of the virion, which is called the surface antigens (HBsAg), and is
produced in excess during the life cycle of the virus.[
Causes
Hepatitis B infection is caused by the hepatitis B virus (HBV). The virus is passed from person
to person through blood, semen or other body fluids. It does not spread by sneezing or coughing.

Common ways that HBV can spread are:

 Sexual contact. You may get hepatitis B if you have unprotected sex with someone who is
infected. The virus can pass to you if the person's blood, saliva, semen or vaginal secretions
enter your body.
 Sharing of needles. HBV easily spreads through needles and syringes contaminated with
infected blood. Sharing IV drug paraphernalia puts you at high risk of hepatitis B.
 Accidental needle sticks. Hepatitis B is a concern for health care workers and anyone else who
comes in contact with human blood.
 Mother to child. Pregnant women infected with HBV can pass the virus to their babies during
childbirth. However, the newborn can be vaccinated to avoid getting infected in almost all cases.
Talk to your doctor about being tested for hepatitis B if you are pregnant or want to become
pregnant.

Acute vs. chronic hepatitis B

Hepatitis B infection may be either short-lived (acute) or long lasting (chronic).

 Acute hepatitis B infection lasts less than six months. Your immune system likely can clear acute
hepatitis B from your body, and you should recover completely within a few months. Most
people who get hepatitis B as adults have an acute infection, but it can lead to chronic infection.
 Chronic hepatitis B infection lasts six months or longer. It lingers because your immune system
can't fight off the infection. Chronic hepatitis B infection may last a lifetime, possibly leading to
serious illnesses such as cirrhosis and liver cancer.

The younger you are when you get hepatitis B — particularly newborns or children younger than
5 — the higher your risk of the infection becoming chronic. Chronic infection may go undetected
for decades until a person becomes seriously ill from liver disease.

Risk factors
Hepatitis B spreads through contact with blood, semen or other body fluids from an infected
person. Your risk of hepatitis B infection increases if you:

 Have unprotected sex with multiple sex partners or with someone who's infected with HBV
 Share needles during IV drug use
 Are a man who has sex with other men
 Live with someone who has a chronic HBV infection
 Are an infant born to an infected mother
 Have a job that exposes you to human blood
  Travel to regions with high infection rates of HBV, such as Asia, the Pacific Islands, Africa and
Eastern Europe

Complications
Having a chronic HBV infection can lead to serious complications, such as:

 Scarring of the liver (cirrhosis). The inflammation associated with a hepatitis B infection can
lead to extensive liver scarring (cirrhosis), which may impair the liver's ability to function.
 Liver cancer. People with chronic hepatitis B infection have an increased risk of liver cancer.
 Liver failure. Acute liver failure is a condition in which the vital functions of the liver shut down.
When that occurs, a liver transplant is necessary to sustain life.
 Other conditions. People with chronic hepatitis B may develop kidney disease or inflammation
of blood vessels.

 Pathogenesis
 Hepatitis B virus is dangerous because it attacks the liver, thus inhibiting the
functions of this vital organ. The virus causes persistent infection, chronic
hepatitis, liver cirrhosis, hepatocellular carcinoma, and immune complex disease.
 HBV infection in itself does not lead to the death of infected hepatocytes. HBV in
a non-cytolytic infection. Liver damage however, arises from cytolytic effects of
the immune system's cytotoxic T lymphocytes (CTL) which attempt to clear
infection by killing infected cells. The strength of the CTL response has been
noted to determine the course of the infection. For example, a vigorous CTL
response results in clearance and recovery, although often with an episode of
jaundice. A weak response results in few symptoms and chronic infection (and
hence higher susceptibility for hepatocellular carcinoma).
 The younger a person is when she becomes infected with HBV, the more likely
she is to be asymptomatic and become a chronic carrier of the disease. Babies
born to infected mothers are at very high risk of to becoming carriers and
developing liver pathology.
 Vertical is thus one common way that HBV is transmitted, along with
transmission through sexual intercourse and mixing of blood products. Vertical
transmission can be prevented by administering vaccine the same day of birth.
Different modes of transmission are more prevalent in certain areas of the world
and among certain high-risk groups, yet all areas of the world see HBV
transmission through all of these avenues. About 90% of adults who acquire HBV
recover from it completely and become immune to the virus. The other 10% of
cases are the people who become chronic carriers.
Chronic infection with the hepatitis B virus (HBV) is a major risk factor for development of hepatocellular
carcinoma (HCC). The pathogenesis of cancer in HBV infection has been extensively analyzed, and
multiple factors appear to play a role. A major factor is chronic inflammation and the effects of
cytokines in the development of fibrosis and liver cell proliferation. Also important is the role of
integration of HBV DNA into host cellular DNA, which, in some situations, acts to disrupt or promote
expression of cellular genes that are important in cell growth and differentiation. In addition, expression
of HBV proteins may have a direct effect on cellular functions, and some of these gene products can
favor malignant transformation. Several HBV genes have been found in infected tissues more frequently
than others, including truncated pre-S2/S, hepatitis B X gene, and a novel spliced transcript of HBV,
referred to as the hepatitis B spliced protein. The proteins expressed from these integrated genes have
been shown to have intracellular activities that may account for their association with HCC, including
effects on cellular growth and apoptosis. Finally, some patients with HCC have no detectable hepatitis B
surface antigen in serum but do have low levels of HBV DNA in serum and integrated molecules of HBV
DNA in tissue. Occult HBV infection may account for a proportion of cases of HCC that occur in patients
without serologic markers for hepatitis B and C and may be a cofactor in HCC in patients with chronic
hepatitis C who have coexistent occult HBV infection.
reatment
There's no cure for HIV/AIDS, but many different drugs are available to control the virus. Such
treatment is called antiretroviral therapy, or ART. Each class of drug blocks the virus in different
ways. ART is now recommended for everyone, regardless of CD4 T cell counts. It's
recommended to combine three drugs from two classes to avoid creating drug-resistant strains of
HIV.

The classes of anti-HIV drugs include:

 Non-nucleoside reverse transcriptase inhibitors (NNRTIs) turn off a protein needed

by HIV to make copies of itself. Examples include efavirenz (Sustiva), etravirine
(Intelence) and nevirapine (Viramune).
 Nucleoside or nucleotide reverse transcriptase inhibitors (NRTIs) are faulty versions
of the building blocks that HIV needs to make copies of itself. Examples include
Abacavir (Ziagen), and the combination drugs emtricitabine/tenofovir (Truvada),
Descovy (tenofovir alafenamide/emtricitabine), and lamivudine-zidovudine (Combivir).
 Protease inhibitors (PIs) inactivate HIV protease, another protein that HIV needs to
make copies of itself. Examples include atazanavir (Reyataz), darunavir (Prezista),
fosamprenavir (Lexiva) and indinavir (Crixivan).
 Entry or fusion inhibitors Tblock HIV's entry into CD4 T cells. Examples include
enfuvirtide (Fuzeon) and maraviroc (Selzentry).
 Integrase inhibitors work by disabling a protein called integrase, which HIV uses to
insert its genetic material into CD4 T cells. Examples include raltegravir (Isentress) and
dolutegravir (Tivica